This is a proposal to conduct a series of studies on the clinical pharmacology of levo-alpha acetylmethadol (LAAM), which are directly relevant to its safety and clinical efficacy as an opiate maintenance/detoxification agent. Using within- and between-subject experimental designs, these studies will be conducted under rigorously controlled, double-blind conditions. Healthy adult volunteers, who are either opioid-dependent or opioid-experienced, will participate in these studies as inpatients on a residential research laboratory. The broad clinical issues to be addressed include characterization of the acute pharmacodynamic properties of LAAM, assessment of the opioid blockade properties of LAAM, and evaluation of various LAAM induction procedures. Specifically, the first study will assess the acute pharmacodynamic properties of LAAM when given orally and intravenously, and will provide information regarding safety, dose-effects, time course, and parenteral abuse liability. The second study will assess the development of cross- tolerance in response to LAAM maintenance, with a particular emphasis on the duration of blockade and the dose response relationships. The third study will characterize the time course and magnitude of withdrawal symptoms during transition from a short-acting opioid to LAAM, using the current FDA recommended dosing schedule for induction. The fourth study will characterize the crossover from methadone to LAAM in order to assess the therapeutic value of short-term methadone treatment prior to LAAM induction in unstabilized heroin addicts, and to assess the efficacy, safety and patient acceptability of the current induction schedule of LAAM in methadone-maintained patients. In summary, these studies will provide information on the pharmacodynamic properties of LAAM relevant to its clinical utility, efficacy and safety as a pharmacological adjunct for the treatment of intravenous opioid abusers. The development of new and effective pharmacotherapies for substance abuse, such as LAAM, will serve to reduce the medical complications stemming from intravenous drug abuse, including a reduction in the spread of HIV infection and AIDS.